The broad objective of this project is to gain further understanding of hormonal mechanisms governing reproductive processes in women which will provide the foundation for clinical therapies directed toward reproductive disorders such as endometriosis, pregnancy loss, fertility, and estrogen-dependent reproductive neoplasms. We have approached this objective by the study of proteins responsible for mediating and/or modulating estrogen-dependent reproductive processes. Advances during the current period include: 1) sequencing and initial characterization of a novel estrogen receptor binding protein; 2) demonstration that the novel gene is expressed in hormonally responsive reproductive tissues such as ovary, breast, and endometrium; 3) demonstration that the novel protein interacts specifically with the estrogen receptor in vitro; 4) demonstration that overexpression of the protein markedly influences estrogen receptor function; 5) demonstration that interaction between the novel protein and the estrogen receptor requires discrete regions of the estrogen receptor as well as distinct regions of the novel receptor-binding protein. Given the central role of estrogen in reproduction, we plan to continue to concentrate effort on delineation of the possible role of this gene in the regulation of hormonally dependent reproductive processes.